Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000666609 | SCV000790928 | uncertain significance | Nemaline myopathy 2 | 2017-04-14 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001553645 | SCV001774580 | likely pathogenic | Nemaline myopathy | 2023-08-16 | criteria provided, single submitter | clinical testing | Variant summary: NEB c.4337G>T (p.Gly1446Val) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 249100 control chromosomes (gnomAD). c.4337G>T has been reported in the literature as a compound heterozygous genotype with other deleterious variants in at least three unique individuals affected with Nemaline Myopathy 2 (e.g., Lehtokari_2014, Hindocha_2017). At least one of these individuals was comprehensively phenotyped with features of congenital nemaline myopathy co-presenting with systemic lupus erythematosus (Hindocha_2017). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 28977494, 25205138). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Fulgent Genetics, |
RCV005027784 | SCV005652525 | likely pathogenic | Nemaline myopathy 2; Arthrogryposis multiplex congenita 6 | 2024-03-01 | criteria provided, single submitter | clinical testing |